Gut inflammation in AUD and ALD patients
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PROVIDER: PRJEB90453 | ENA |
REPOSITORIES: ENA
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Project description:Morphine and its pharmacological derivatives are the most prescribed analgesics for moderate to severe pain management. However, chronic use of morphine reduces pathogen clearance and induces bacterial translocation across the gut barrier. The enteric microbiome has been shown to play a critical role in the preservation of the mucosal barrier function and metabolic homeostasis. Here, we show for the first time, using bacterial 16s rDNA sequencing, that chronic morphine treatment significantly alters the gut microbial composition and induces preferential expansion of the gram-positive pathogenic and reduction of bile-deconjugating bacterial strains. A significant reduction in both primary and secondary bile acid levels was seen in the gut, but not in the liver with morphine treatment. Morphine induced microbial dysbiosis and gut barrier disruption was rescued by transplanting placebo-treated microbiota into morphine-treated animals, indicating that microbiome modulation could be exploited as a therapeutic strategy for patients using morphine for pain management. In this study, we establish a link between the two phenomena, namely gut barrier compromise and dysregulated bile acid metabolism. We show for the first time that morphine fosters significant gut microbial dysbiosis and disrupts cholesterol/bile acid metabolism. Changes in the gut microbial composition is strongly correlated to disruption in host inflammatory homeostasis13,14 and in many diseases (e.g. cancer/HIV infection), persistent inflammation is known to aid and promote the progression of the primary morbidity. We show here that chronic morphine, gut microbial dysbiosis, disruption of cholesterol/bile acid metabolism and gut inflammation; have a linear correlation. This opens up the prospect of devising minimally invasive adjunct treatment strategies involving microbiome and bile acid modulation and thus bringing down morphine-mediated inflammation in the host.
2016-06-01 | E-MTAB-3722 | biostudies-arrayexpress
Project description:X-linked adrenoleukodystrophy (X-ALD) is a metabolic genetic disorder of the central nervous system characterized by axonopathy in spinal cords, progressive demyelination in the brain and adrenal insufficiency. Here we provide transcriptomic data from white matter of human X-ALD patients compared to healthy individuals. In particular, from two different disease variants: 1) patients with adrenomyeloneuropathy (AMN) with cerebral demyelination (cAMN) and, 2), an acute, ultimately lethal childhood cerebral form (cALD) featuring severe demyelination in the brain.
2012-03-21 | E-MEXP-3288 | biostudies-arrayexpress
Project description:Application of a mass spectrometry -based approach to investigate if bacterial translocation from gut microbiota could take part in the chronic inflammation observed in Rheumatoid Arthritis patients
2025-05-06 | PXD045023 | Pride
Project description:Adrenoleukodystrophy (ALD) is a rare X-linked neurogenetic disease caused by mutations in the ABCD1 gene. Currently, the molecular mechanisms underlying the onset and severity of ALD still remain unclear. For mining information on candidate genes associated with onset and severity of ALD, RNA-seq had been executed via using whole blood samples from monozygotic twin families with ALD disease. The information on candidate genes of this research had been considered as the crucial for preliminarily exploring the molecular mechanisms relating to the onset and severity of ALD, which offered novel insights and research directions for mitigating and treating the development of ALD.
2024-09-06 | GSE276153 | GEO
Project description:While fermentable oligo- and di-, mono-saccharides and polyols (FODMAPs) have been implicated in exacerbating inflammatory bowel disease (IBD) symptoms, the exact influence of FODMAPs on gut microbiota and inflammation is unclear. Here, we show that sorbitol, a polyol, exacerbates colitis in mice induced by dextran sodium sulfate (DSS). Sorbitol increases the expression of inflammatory genes including Il1b in the colon, associated with M1 macrophage-related genes elevated in IBD patients. Indeed, sorbitol treatment leads to a higher proportion of M1 macrophages in the colon, worsening colitis, which is reversed in IL-1β-deficient mice and mitigated with antibiotic treatment. Sorbitol alters the composition of gut microbiota and metabolites, with Prevotellaceae and tryptamine positively correlated with colonic M1 macrophages. Tryptamine stimulation enhances M1 macrophage polarization. Taken together, polyol consumption activates intestinal macrophages by altering the gut microbiome, which in turn promotes intestinal inflammation.
2025-06-14 | GSE299433 | GEO
Project description:This study aims to investigate the role of gut microbiome pattern and inflammation marker NF-ҡB in young-onset colorectal cancer
| 2310315 | ecrin-mdr-crc
Project description:X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder characterized by axonopathy and demyelination in the central nervous system and adrenal insufficiency. Main X-ALD phenotypes are: (i) an adult adrenomyeloneuropathy (AMN) with axonopathy in spinal cords, (ii) cerebral AMN with brain demyelination (cAMN) and (iii) a childhood variant, cALD, characterized by severe cerebral demyelination. Loss of function of the ABCD1 peroxisomal fatty acid transporter and subsequent accumulation of very-long-chain fatty acids (VLCFAs) are the common culprits to all forms of X-ALD, an aberrant microglial activation accounts for the cerebral forms. How same mutation in the ABCD1 gene can lead to clinically very distinct phenotypes and what factors account for the dissimilar clinical outcomes and prognosis of X-ALD variants remain elusive. We wonder whether epigenetics mechanisms could answer the lack of genotype-phenotype correlation. We employed Illumina state of the art technology to analyze the differential methylation of over 485,000 CpG sites throughout the entire human genome and used stringent statistical criteria to define differential methylation patterns between brains of cALD, cAMN and age-matched controls. We identified a common X-ALD methylation signature comprising the hypermethylation in genes harboring the trimethylated histone H3K27me3 mark in their promoters, the hypermethylation for genes driven the oligodendrocyte lineage, and the hypomethylation for immune-associated genes. We also examined the methylated differences between cALD and cAMN resulting with differential immune response pathways and concordance methylation levels with phenotype severity. The detected methylation differences correlated with transcriptional and translational consequences, as supported by Affymetrix expression arrays, quantitative PCR and WB changes. The reliability of these changes was further demonstrated by validating DNA methylation by an independent pyrosequencing assay. From these evidences, we propose the altered transcriptional programs in oligodendrocyte differentiation in X-ALD patients. These observations may provide new therapeutic epigenetic agents.
2019-02-01 | GSE78218 | GEO
Project description:BACKGROUND & AIMS: There is mounting evidence that microbes resident in the human intestine contribute to diverse alcohol-associated liver diseases (ALD) including the most deadly form known as alcoholic hepatitis (AH). However, mechanisms by which gut microbiota synergize with excessive alcohol intake to promote liver injury are poorly understood. Furthermore, whether drugs that selectively target gut microbial metabolism can improve ALD has never been tested. METHODS: We used liquid chromatography tandem mass spectrometry to quantify the levels of microbe and host choline co-metabolites in healthy controls and AH patients, and identified the metabolite trimethylamine (TMA) as a gut microbe-derived biomarker of AH. In subsequent studies, we treated mice with non-lethal mechanism-based bacterial choline TMA lyase inhibitors to blunt gut microbe-dependent production of TMA in the context of chronic ethanol administration. Indices of liver injury were quantified by complementary RNA sequencing, biochemical, and histological approaches. In addition, we examined the impact of ethanol consumption and TMA lyase inhibition on gut microbiome structure via 16S rRNA sequencing. RESULTS: We show the gut microbial choline metabolite trimethylamine (TMA) is elevated in AH patients, which is correlated with reduced hepatic expression of the TMA oxygenase flavin-containing monooxygenase 3 (FMO3). Provocatively, we find that small molecule inhibition of gut microbial choline TMA lyase activity protects mice from ethanol-induced liver injury. TMA lyase inhibitor-driven improvement in ethanol-induced liver injury is associated with distinct reorganization of the gut microbiome community and host liver transcriptome. CONCLUSIONS: The microbial metabolite TMA is a biomarker of AH, and blocking TMA production from gut microbes can blunt ALD in mice.
2021-03-31 | GSE157681 | GEO
Project description:A phylogenetic microarray targeting 66 families described in the human gut microbiota has been developped aud used to monitor the gut microbiota's structure and diversity. The microarray format provided by Agilent and used in this study is 8x15K. A study with a total of 4 chips was realized.
2013-03-01 | GSE44752 | GEO
Project description:Spiroplasma sp. sAld-Tx isolate:ald Genome sequencing and assembly
| PRJNA506491 | ENA